Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, China.
Nanoscale. 2018 May 10;10(18):8628-8641. doi: 10.1039/c7nr09083h.
Since conventional chemotherapy is a systemic treatment that affects the body globally and will not concentrate inside the tumor, it causes adverse side effects to patients. In this study, doxorubicin (DOX) together with solid gold nanoparticles (GNPs) or hollow gold nanoparticles (HGNPs), respectively, is loaded inside thermosensitive liposomes (GNPs&DOX-TLs and HGNPs&DOX-TLs), where the GNPs and HGNPs act as a "nanoswitch" for killing tumor cells directly by hyperthermia and triggering DOX release from TLs in the tumor quickly by near infrared laser (NIR) illumination. In addition, this study investigated the photothermal transformation ability, NIR triggered drug release behavior, and the intracellular uptake and cytotoxicity of breast tumor cells and the thermo-chemotherapy mediated by the co-delivery of GNPs&DOX-TLs and HGNPs&DOX-TLs. GNPs and HGNPs had very different light-to-heat transduction efficiencies, while the hollow HGNPs had the advantage of NIR surface plasmon tunability, resulting in the photothermal ablation of tumors with 800 nm light penetration in tissue. The prepared HGNPs&DOX-TLs exhibited a spherical shape with a diameter of 190 nm and a ξ potential of -29 mV, which were steadily dispersed for at least one month. The co-encapsulated DOX was released under hyperthermia caused by NIR-responsive HGNPs and the local drug concentration increased along with the disintegration of the liposomal membrane. This co-delivery of HGNPs&DOX-TLs produced a synergistic cytotoxicity response, thereby enhancing anticancer efficacy 8-fold and increasing the survival time compared to GNPs&DOX-TLs. This work suggested that the co-delivery of HGNPs&DOX-TLs followed by burst-release of DOX using NIR-responsive HGNPs sensitized cancer cells to the chemotherapeutic compound, which provided a novel concept for the combination strategy of chemotherapy and photothermal therapy. These results suggest that the markedly improved therapeutic efficacy and decreased systemic toxicity of the NPs presented in this study hold significant potential for future cancer treatment.
由于传统化疗是一种全身性治疗，会对全身产生影响，而不会集中在肿瘤内，因此会给患者带来不良反应。在本研究中，阿霉素（DOX）分别与实心金纳米颗粒（GNPs）或空心金纳米颗粒（HGNPs）一起装载在热敏脂质体（GNPs&DOX-TLs 和 HGNPs&DOX-TLs）中，其中 GNPs 和 HGNPs 充当“纳米开关”，通过热疗直接杀死肿瘤细胞，并通过近红外激光（NIR）照射快速触发 TL 中 DOX 的释放。此外，本研究还研究了载金纳米颗粒&DOX-TLs 和载空心金纳米颗粒&DOX-TLs 的共递药系统的光热转换能力、NIR 触发的药物释放行为以及乳腺癌细胞的细胞内摄取和细胞毒性，以及热化疗。GNPs 和 HGNPs 具有非常不同的光热转换效率，而空心 HGNPs 具有近红外表面等离子体可调谐性的优势，从而实现了组织中 800nm 光穿透的肿瘤光热消融。所制备的 HGNPs&DOX-TLs 呈球形，直径为 190nm，ξ 电位为-29mV，至少稳定分散一个月。共包封的 DOX 在 NIR 响应的 HGNPs 引起的热疗下释放，并且随着脂质体膜的崩解，局部药物浓度增加。HGNPs&DOX-TLs 的共递药产生协同细胞毒性反应，从而使抗癌功效提高 8 倍，并与 GNPs&DOX-TLs 相比增加了存活时间。这项工作表明，NIR 响应的 HGNPs 使共递药的 HGNPs&DOX-TLs 释放 DOX 产生爆发式释放，使癌细胞对化疗药物敏感，为化疗和光热治疗的联合策略提供了新的概念。这些结果表明，本研究中所呈现的 NPs 的治疗效果显著提高和系统毒性降低，为未来癌症治疗提供了巨大的潜力。
